WO2023120808A1 - Procédé de fabrication de timbre à micro-aiguilles - Google Patents

Procédé de fabrication de timbre à micro-aiguilles Download PDF

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Publication number
WO2023120808A1
WO2023120808A1 PCT/KR2022/001927 KR2022001927W WO2023120808A1 WO 2023120808 A1 WO2023120808 A1 WO 2023120808A1 KR 2022001927 W KR2022001927 W KR 2022001927W WO 2023120808 A1 WO2023120808 A1 WO 2023120808A1
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WO
WIPO (PCT)
Prior art keywords
base material
core
active ingredient
microneedle
cover
Prior art date
Application number
PCT/KR2022/001927
Other languages
English (en)
Korean (ko)
Inventor
전이슬
이재준
배태근
이인덕
Original Assignee
주식회사 페로카
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 주식회사 페로카 filed Critical 주식회사 페로카
Publication of WO2023120808A1 publication Critical patent/WO2023120808A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/30—Mounting, exchanging or centering
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/30—Mounting, exchanging or centering
    • B29C33/301—Modular mould systems [MMS], i.e. moulds built up by stacking mould elements, e.g. plates, blocks, rods
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/44—Moulds or cores; Details thereof or accessories therefor with means for, or specially constructed to facilitate, the removal of articles, e.g. of undercut articles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053—Methods for producing microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/02—General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0244—Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2207/00—Methods of manufacture, assembly or production

Definitions

  • the present invention relates to a method for manufacturing a microneedle patch.
  • Drug injection into the human body has traditionally been performed by needle injection, but needle injection causes great pain. Therefore, a non-invasive drug injection method has also been developed, but there is a problem in that the amount of drug required is too large compared to the amount of injection.
  • DDS drug delivery system
  • microneedles can be characterized by painless skin penetration and no trauma.
  • a certain degree of physical hardness may be required because the microneedle must penetrate the stratum corneum of the skin.
  • an appropriate length may be required in order for the physiologically active material to reach the epidermal layer or the dermal layer of the skin.
  • the skin permeability of the "micro" needles must be high and maintained for a certain period of time until they are dissolved after being inserted into the skin.
  • microneedles capable of delivering a drug in a precise amount and accurately setting a target position is increasing.
  • the present invention can effectively deliver active ingredients to a target location and can provide a method for manufacturing a microneedle patch having a multi-layered structure in a radial direction.
  • the steps of injecting a first base material into a first mold, forming a core by curing the first base material, inserting the core into a second mold, and A method for manufacturing a microneedle patch comprising injecting a second base material into a mold and forming a cover disposed outside the core by curing the second base material.
  • the method for manufacturing a microneedle patch according to the present invention can manufacture a microneedle having a plurality of layers in a radial direction. Since the core is first manufactured and then the cover is formed outside the core, strength and durability of the microneedle can be increased.
  • the adhesive force between the microneedle and the mold is reduced due to the contraction of the microneedle, so that a high-quality microneedle patch can be manufactured.
  • FIG. 1 is a perspective view showing a microneedle patch according to an embodiment of the present invention.
  • FIG. 2 is a cross-sectional view of the microneedle arrangement of FIG. 1 .
  • FIG. 3 is an enlarged view of a part of FIG. 2 .
  • FIG. 4 to 8 are views showing modified examples of FIG. 3 .
  • FIG. 9 is a flowchart illustrating a method of manufacturing a microneedle patch according to another embodiment of the present invention.
  • 10 to 12 are diagrams illustrating the method of manufacturing the microneedle patch of FIG. 9 .
  • FIG. 13 is a flowchart illustrating a method of manufacturing a microneedle patch according to another embodiment of the present invention.
  • FIG. 14 and 15 are views illustrating the method of manufacturing the microneedle patch of FIG. 13 .
  • the steps of injecting a first base material into a first mold, forming a core by curing the first base material, inserting the core into a second mold, and A method for manufacturing a microneedle patch comprising injecting a second base material into a mold and forming a cover disposed outside the core by curing the second base material.
  • the core may include a first active ingredient
  • the cover may include a second active ingredient that is activated together with the first active ingredient or increases the activity of the first active ingredient.
  • the first base material may shrink and harden so that the adhesive force between the first base material and the surface of the first mold may decrease.
  • the second base material may shrink and harden, so that the adhesive force between the second base material and the surface of the second mold may decrease.
  • the second base material may cover the outside of the core so that it is not exposed to the outside.
  • Another aspect of the present invention includes the steps of injecting a first base material into a first mold, forming a core by curing the first base material, and injecting a second base material into a second mold; Forming a cover having an insertion groove by curing the second base material; and inserting the core into the insertion groove of the cover.
  • the step of inserting the core into the cover may further include applying an intermediate material to an outer surface of the core or an inner surface of the insertion groove.
  • the core may include a first active ingredient
  • the cover may include a second active ingredient that is activated together with the first active ingredient or increases the activity of the first active ingredient.
  • the second base material may cover the outside of the core so that it is not exposed to the outside.
  • FIG. 1 is a perspective view showing a microneedle patch according to an embodiment of the present invention
  • FIG. 2 is a view showing a cross-section of the microneedle arrangement of FIG. 1
  • FIG. 3 is an enlarged view of a portion of FIG. 2 am.
  • the microneedle patch 100 may include a base 110 and a microneedle 120 .
  • the base 110 supports the microneedles 120 and may have a plurality of microneedles 120 on one surface. One side of the base 110 may be in contact with the skin, and the other side of the base 110 may be exposed to the outside.
  • the base 110 may be removed when the microneedle 120 is implanted into the skin.
  • the base may be removed from the skin by applying force by the user.
  • a portion where the base 110 and the microneedle 120 are connected is first dissolved, and the base 110 may be removed after a predetermined time has elapsed after attachment.
  • the base 110 when the microneedle patch 100 is attached for a long time, the base 110 may be dissolved. As another example, the base 110 may be removed by a user applying a material for dissolution.
  • the base 110 may include any one of the materials included in the microneedle 120 .
  • the base 110 may include a biodegradable material like the microneedle 120 .
  • the base 110 may include the same material as any one of the core 121 and the cover 122 of the microneedle 120 .
  • the base 110 may include a physiologically active material. After attaching the microneedle patch 100 to the skin, an effective drug can be effectively delivered to the patient by the physiologically active substance coming out of the base 110. In addition, the base 110 and the microneedle 120 can be easily separated by the physiologically active substance coming out of the base 110 .
  • the base 110 may include a water-soluble polymer.
  • the base 110 may be composed of a water-soluble polymer or may contain other additives (eg, disaccharides).
  • the base 110 preferably does not contain drugs or active ingredients.
  • Base 110 may include a biocompatible material.
  • the base 110 may select a biocompatible material selected as a base material of the microneedle 120 to be described later as a base material.
  • the microneedles 120 protrude from the surface of the base 110 and may be provided in plurality.
  • the microneedle 120 may be formed of a biocompatible material and an additive.
  • Biocompatible materials include carboxymethyl cellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate, dex Tran Sulfate, Chitosan, Polylysine, Carboxymethyl Chitin, Fibrin, Agarose, Pullulan, Polyanhydride , polyorthoester, polyetherester, polyesteramide, poly butyric acid, poly valeric acid, polyacrylate, Ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, polyvinyl chloride, polyvinyl fluoride, polyvinyl imidazole, chlorosulphonate polyolefins , polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethylcellulose, cyclodextrin (Cyclodextrin),
  • the additives are trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid, alginic Alginic acid, Pectin, Carrageenan, Chondroitin Sulfate, Dextran Sulfate, Chitosan, Polylysine, Collagen, Gelatin, Carboxymethyl Chitin ( carboxymethyl chitin), fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), Hydroxypropylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentiobiose, alkyltrimethylammonium bromide (Cetrimide), hexadecyltrimethylammoniumbromide (CTAB) , Gentian Violet, benzethonium chloride, docus
  • Hyaluronic acid is used to include not only hyaluronic acid but also hyaluronic acid salts (eg, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate and calcium hyaluronate) and mixtures thereof.
  • Hyaluronic acid is used as a meaning including cross-linked hyaluronic acid and/or non-cross-linked hyaluronic acid.
  • the hyaluronic acid of the present invention has a molecular weight of 2 kDa to 5000 kDa.
  • the hyaluronic acid of the present invention has a molecular weight of 100-4500, 150-3500, 200-2500 kDa, 220-1500 kDa, 240-1000 kDa or 240-490 kDa.
  • Carboxymethyl cellulose may use CMC of various known molecular weights.
  • the average molecular weight of CMC used in the present invention is 90,000 kDa, 250,000 kDa or 700,000 kDa.
  • the disaccharide may include sucrose, lactulose, lactose, maltose, trehalose, or cellobiose, and may include sucrose, maltose, or trehalose in particular.
  • an adhesive may be included.
  • the adhesive is at least one adhesive selected from the group consisting of silicone, polyurethane, hyaluronic acid, physical adhesive (Gecko), poly acrylic, ethyl cellulose, hydroxy methyl cellulose, ethylene vinyl acetate and polyisobutylene.
  • the microneedle 120 may additionally include metal, a high molecular weight polymer, or an adhesive.
  • the microneedle 120 may contain an active ingredient (EM). At least a portion of the microneedle 120 may include a pharmaceutical, medical or cosmetic active ingredient (EM).
  • active ingredients include, but are not limited to, protein/peptide drugs, hormones, hormone analogues, enzymes, enzyme inhibitors, signaling proteins or parts thereof, antibodies or parts thereof, single chain antibodies, binding It includes at least one of proteins or binding domains thereof, antigens, adhesion proteins, structural proteins, regulatory proteins, toxin proteins, cytokines, transcriptional regulators, blood coagulation factors, and vaccines.
  • the protein / peptide drug is insulin, IGF- 1 (insulinlike growth factor 1), growth hormone, erythropoietin, G-CSFs (granulocyte-colony stimulating factors), GM-CSFs (granulocyte / macrophage- colony stimulating factors), interferon alpha, interferon beta, interferon gamma, interleukin-1 alpha and beta, interleukin-3, interleukin-4, interleukin-6, interleukin-2, epidermal growth factors (EGFs), calcitonin , adrenocorticotropic hormone (ACTH), tumor necrosis factor (TNF), atobisban, buserelin, cetrorelix, deslorelin, desmopressin , dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, growth hormone releasing hormone-II (GHRHII), gonadorelin ), goserelin, his
  • the active ingredient (EM) may be a colloid dispersed in a solvent forming the microneedles 120 in the form of particulates.
  • the fine particles themselves may be an active ingredient (EM) or may include a coating material carrying the active ingredient (EM).
  • the active ingredient (EM) may be intensively distributed in a partial area of the microneedle 120 . That is, since the active ingredient EM is disposed at a specific height or a specific depth in the microneedle 120, the active ingredient EM can be effectively delivered.
  • the active ingredient (EM) may be dissolved in the microneedle 120 .
  • the active ingredient (EM) may be dissolved in a base material of the microneedle 120 such as the aforementioned biodegradable materials to form the microneedle 120 .
  • the active ingredient (EM) may be dissolved in the base material at a uniform concentration and may be intensively distributed at a specific height or depth of the microneedle 120 like the above-described fine particles.
  • the microneedle patch 100 may have a plurality of active ingredients (EM) according to regions.
  • EM active ingredients
  • a microneedle of a first group contains a first active ingredient among the plurality of active ingredients
  • a microneedle of a second group different from the first group contains a second active ingredient among the plurality of active ingredients.
  • a pharmaceutical, medical or cosmetic active ingredient may be coated on the microneedle 120 .
  • the active ingredients (EM) may be coated on the entire microneedle 120 or only a portion of the microneedle 120 .
  • a portion of the coating layer of the microneedle 120 may be coated with the first active ingredient, and the other portion may be coated with the second active ingredient.
  • the microneedle 120 may be elongated. Since the microneedle 120 has a predetermined length, the drug can be delivered to a deep location in the skin.
  • the microneedle 120 may have a core 121 and a cover 122 . Since the cover 122 is disposed outside the core 121, the microneedle 120 may have a multi-layered structure in the radial direction.
  • the core 121 extends along the central axis of the microneedle 120 and may have a predetermined length.
  • the core 121 may have various shapes.
  • the core 121 may have a cylindrical or polygonal column shape as shown in FIG. 3 .
  • the core 121 extends in the insertion direction of the microneedle 120 and has a predetermined rigidity, it is stably inserted when inserted into the skin, and the microneedle patch 100 can be maintained in an attached state.
  • the core 121 may be disposed such that one end contacts the base 110 and the other end faces a sharpened tip (ST) of the core.
  • the core may be disposed such that one end is inserted into the base and the other end faces the tip ST.
  • the core may be disposed in an inner space of the cover with one end spaced apart from the base.
  • the cover 122 may cover the outside of the core 121 .
  • the cover 122 may cover the outside so that the core 121 is not exposed to the outside.
  • the cover 122 may have an extension portion 122A extending along the core 121 and a tip portion 122B disposed at an end of the extension portion 122A to form a tip tip ST.
  • the core 121 may be formed of a first base material that is a biocompatible material
  • the cover 122 may be formed of a second base material that is a biocompatible material.
  • the first base material and the second base material may be selected from the aforementioned biocompatible materials.
  • the first base material and the second base material may be different biocompatible materials. Since the first base material and the second base material are different from each other, the core 121 and the cover 122 may have different physical and pharmaceutical properties.
  • the core 121 may have greater rigidity than the cover 122 . Since the core 121 has relatively high rigidity, the elongated microneedle 120 can be stably inserted into the skin.
  • the first base material and the second base material may be the same biocompatible material. Since the core 121 and the cover 122 are formed of the same base material, a strong bond can be maintained at the connected portion.
  • the microneedle 120 may have the above-described active ingredient (EM).
  • the cover 122 includes an active ingredient (EM), and when the microneedle 120 is attached to the skin, the active ingredient (EM) can be activated while the cover 122 is decomposed.
  • the microneedle patch 100 has a core 121 extending along the longitudinal direction, so that the microneedle 120 can be implanted deep into the skin. Since the core 121 has a predetermined rigidity, the user can effectively attach the microneedle patch 100 to the skin without damaging the microneedle 120 when attaching it to the skin.
  • the microneedle patch 100 has the active ingredient (EM) in the microneedle 120
  • the active ingredient (EM) can be delivered to the skin.
  • the microneedles 120 have a layered structure in the radial direction, the same active ingredient can be delivered to the skin during a set time during which the microneedles 120 are implanted into the skin and the cover 122 is disassembled.
  • FIG. 4 to 8 are views showing modified examples of FIG. 3 .
  • the microneedle patch 100A may have a base 110 and microneedles 120A.
  • the microneedle 120A may have a core 121A and a cover 122A.
  • the microneedle 120A has a characteristic of an active ingredient, and hereinafter, this will be mainly described.
  • the core 121A may be formed of a first base material, and the first active ingredient EM1 may be disposed therein. In one embodiment, the first active ingredient EM1 may be evenly distributed in the core 121A. In another embodiment, the first active ingredient EM1 may be densely disposed at a specific height of the core 121A.
  • the cover 122A may be formed of a second base material, and the second active ingredient EM2 may be disposed therein.
  • the second active ingredient EM2 may be evenly distributed on the cover 122A.
  • the second active ingredient EM2 may be densely disposed at a specific height of the cover 122A or densely disposed at the apical tip.
  • the second active ingredient EM2 is delivered into the skin.
  • the decomposition of the cover 122A ends, the decomposition of the core 121A starts, and the first active ingredient EM1 can be delivered into the skin.
  • the first active ingredient (EM1) may be activated together with the second active ingredient (EM2). While the second active ingredient (EM2) remains in the skin, the first active ingredient (EM1) can be activated together with the second active ingredient (EM2).
  • the activity of the first active ingredient EM1 may be increased by the second active ingredient EM2. That is, when the first active ingredient EM1 is delivered into the skin while the second active ingredient EM2 remains in the skin, the activity of the first active ingredient EM1 can be amplified.
  • the second active ingredient (EM2) may be a substance that promotes the activity of the first active ingredient (EM1).
  • the second active ingredient (EM2) may be any one of various enzymes that degrade the extracellular matrix (ECM).
  • the second active ingredient EM2 flows into the body from the cover 122A and decomposes the extracellular matrix in the body, so that the first active ingredient EM1 is effectively absorbed into the body.
  • the absorption rate of the first active ingredient (EM1) can be increased by decomposing the extracellular matrix in the body of the second active ingredient (EM2).
  • the activity-promoting substance (APM) may be hyaluronidase, an enzyme that degrades or cleaves hyaluronic acid as an extracellular matrix.
  • At least one of the mass per unit volume, the number of moles per unit volume, and the volume per unit volume of the second active ingredient (EM2) may be smaller than that of the first active ingredient (EM1).
  • the unit volume may refer to a unit volume of an area where the first active ingredient EM1 and the second active ingredient EM2 are disposed in the microneedle patch 100, for example, the microneedle 120.
  • the mass per unit volume, the number of moles per unit volume, and the volume per unit volume mean the mass, number of moles, and volume of the first active ingredient EM1 and the second active ingredient EM2 per unit volume of the microneedle 120, respectively.
  • the first active ingredient (EM1) may occupy a greater weight than the second active ingredient (EM2).
  • the weight of the first active ingredient (EM1) may be 5 to 20 times the weight of the second active ingredient (EM2).
  • the weight of the first active ingredient (EM1) may be 10 to 12 times the weight of the second active ingredient (EM2).
  • the second active ingredient (EM2) may excessively degrade the patient's extracellular matrix and damage the user's cells. , may interfere with the absorption of the first active ingredient (EM1). If the weight of the first active ingredient (EM1) is greater than 20 times that of the second active ingredient (EM2), the second active ingredient (EM2) cannot degrade hyaluronic acid in the extracellular matrix, so that the first active ingredient (EM1) not activated effectively.
  • the second active ingredient (EM2) may be activated before the first active ingredient (EM1). That is, in a state where the microneedle 120 is inserted into the body, the second active ingredient EM2 may be delivered into the body before the first active ingredient EM1. Alternatively, in a state where the first active ingredient (EM1) and the second active ingredient (EM2) are delivered into the body, the first active ingredient (EM1) decomposes the extracellular matrix in the body, in particular, after degrading hyaluronic acid. , the first active ingredient (EM1) may react.
  • the microneedle patch 100A has a core 121A extending along the longitudinal direction, so that the microneedle 120A can be implanted in a deep location. Since the core 121A has a predetermined rigidity, the user can effectively attach the microneedle patch 100A to the skin without damaging the microneedle patch 120A.
  • the microneedle patch 100A according to the present invention has an active ingredient in each of the core 121A and the cover 122A, the active ingredient can be sequentially delivered into the skin.
  • the second active ingredient EM2 included in the cover 122A may be delivered into the skin first, and then the first active ingredient EM1 included in the core 121A may be delivered into the skin.
  • the microneedle patch 100B may have a base 110 and microneedles 120B.
  • the microneedle 120B may have a core 121B, a cover 122B and an intermediate layer 123B.
  • the microneedle 120B has a characteristic in the middle layer 123B, and hereinafter, this will be mainly described.
  • the intermediate layer 123B may be disposed between the core 121B and the cover 122B to enhance bonding strength between the core 121B and the cover 122B.
  • the intermediate layer 123B may be formed of a third base material having biocompatibility, adhered to the first base material of the core 121B, and adhered to the second base material of the cover 122B.
  • the middle layer 123B may enhance durability and strength of the microneedle 120B by strengthening the bonding force between the core 121B and the cover 122B.
  • the microneedle patch 100C may have a base and microneedles.
  • the microneedle may have a core 121C, a cover 122C and an intermediate region 123C.
  • the microneedle has a characteristic in the middle region 123C, and hereinafter, this will be mainly described.
  • the middle region 123C may be formed by mixing the first base material BM1 of the core 121C and the second base material BM2 of the cover 122C.
  • the first base material BM1 has a higher ratio than the second base material BM2 in the middle region 123C closer to the core 121C, and closer to the cover 122C the second base material. (BM2) may have a higher ratio than that of the first base material (BM1).
  • the middle region 123C is formed by mixing the first base material BM1 and the second base material BM2, the bonding force between the core 121C and the cover 122C is strengthened to increase durability and strength of the microneedle.
  • the microneedle patch 100D may have a base 110 and microneedles 120D.
  • the microneedle 120D may have a core 121D and a cover 122D.
  • the microneedle 120D is characterized by the layered structure of the cover 122D, which will be mainly described below.
  • the cover 122D may have a multi-layered structure in the radial direction.
  • the cover 122D may be formed of at least two or more layers, and a base material and an active material may be disposed on each layer.
  • a base material and an active material may be disposed on each layer.
  • an embodiment in which the cover 122D includes a first cover layer 1221D and a second cover layer 1222D will be mainly described.
  • the first cover layer 1221D may be disposed to cover the outside of the core 121D, and the second cover layerer 122D may be disposed to cover the outside of the first cover layer 1221D. After disassembly of the outermost second cover layer 1222D is finished, the first cover layer 1221D is disassembled, and then disassembly of the core 121D starts.
  • first cover layer 1221D and the second cover layer 1222D may each have a base material and an active ingredient.
  • the microneedle patch 100D sequentially delivers the active ingredients into the skin over time. can do. Since decomposition progresses gradually from the outermost to the center of the microneedle 120D, various drugs can be delivered by adjusting the decomposition rate of the microneedle 120D.
  • first cover layer 1221D may have a base material
  • second cover layer 1222D may have a base material and an active ingredient
  • the microneedle patch 100D may have a rest period in the middle of drug delivery. .
  • the active ingredient of the second cover layer 1222D is delivered into the skin, the active ingredient of the core 121D is not delivered into the skin until decomposition of the first cover layer 1221D is completed. Since the active ingredient is not additionally transferred during the decomposition process of the first cover layer 1221D, absorption time of the active ingredient of the second cover layer 1222D can be secured.
  • the microneedle patch 100E may have a base 110 and microneedles 120E.
  • the microneedle 120E may have a core 121E and a cover 122E.
  • the microneedle 120E has a characteristic shape, and hereinafter, this will be mainly described.
  • the microneedle 120E may be formed in a cone shape.
  • a cover 122E is disposed outside the core 121E, and the cover 122E may cover a surface of the cone-shaped core 121E so that the core 121E is not exposed to the outside.
  • an active ingredient may be disposed on at least one of the core 121E and the cover 122E. Also, in the microneedle 120E, an intermediate layer or an intermediate region may be formed between the core 121E and the cover 122E.
  • FIG. 9 is a flowchart illustrating a method for manufacturing a microneedle patch according to another embodiment of the present invention
  • FIGS. 10 to 12 are diagrams illustrating the method for manufacturing a microneedle patch of FIG. 9 .
  • the method of manufacturing a microneedle patch includes injecting a first base material into a first mold (S1), curing the first base material to form a core (S2), and forming a core (S2). in a second mold, injecting a second base material into the second mold (S3), and curing the second base material to form a cover disposed outside the core (S4).
  • the first base material BM1 may be injected into the first groove MG1 of the first mold MD1 to form the core 121 . there is. At this time, a base material may be injected to form the base 110 on the top of the first groove MG1 as well.
  • a worker may form a vacuum in the first mold MD1.
  • a suction device (not shown) is disposed under the porous first mold MD1 and the suction device is driven to suck the first base material BM1 to the bottom of the first groove MG1.
  • the first base material BM1 may be filled up to the bottom of the first groove MG1 by centrifugal force by rotating the first mold MD1.
  • step S2 of forming a core by curing the first base material the first base material BM1 may be cured.
  • the first base material BM1 is contracted and cured, so that the adhesive force between the first base material BM1 and the surface of the first mold MD1 may decrease.
  • the first base material BM1 may be dried to form the core 121 .
  • the outer surface of the core 121 moves.
  • the first base material BM1 having fluidity contacts the surface of the first groove MG1 before drying, but when drying proceeds, the first base material BM1 shrinks.
  • the outer surface of the core 121 moves from the 1A surface 121-S1 to the 2A surface 121-S2 by the first contractive force CF1 of the first base material BM1. Since the adhesive force between the dried core 121 and the first mold MD1 decreases, the core 121 can be easily separated from the first mold MD1.
  • the core 121 formed in the first mold MD1 is inserted into the second mold MD2.
  • the second base material BM2 may be injected into the second groove MG2 of the second mold MD2 to fill the outside of the core 121 with the second base material BM2.
  • the second base material BM2 fills the second groove MG2 to a predetermined height.
  • the second base material BM2 may be filled up to a preset height in consideration of the volume of the core 121 .
  • step S4 of curing the second base material to form a cover disposed outside the core the second base material BM2 may be cured.
  • the adhesive force between the second base material and the surface of the second mold MD2 may decrease as the second base material shrinks and hardens.
  • the cover 122 may be formed by drying the second base material BM2 .
  • the outer surface of the cover 122 moves. Referring to FIG. 12 , the second base material BM2 having fluidity comes into contact with the surface of the second groove MG2 before drying, but when drying proceeds, the second base material BM2 shrinks.
  • the outer surface of the cover 122 moves from the 1B surface 122-S1 to the 2B surface 122-S2 by the second contractive force CF2 of the second base material BM2. Since the adhesive force between the dried cover 122 and the second mold MD2 decreases, the cover 122 can be easily separated from the second mold MD2.
  • an intermediate material may be applied to the surface of the core 121 before inserting the core 121 into the second mold MD2 .
  • the core 121 coated with the intermediate material may be inserted into the second mold MD2 , and the second base material BM2 may be disposed outside the intermediate material.
  • the intermediate material may be disposed between the core 121 and the cover 122 to form an intermediate layer.
  • the method for manufacturing a microneedle patch according to the present invention may manufacture a microneedle having a plurality of layers in a radial direction. Since the core 121 is first manufactured and then the cover 122 is formed outside the core 121, strength and durability of the microneedle 120 can be increased.
  • the elongated microneedle is manufactured by injecting a base material into a groove of a mold in order to manufacture a core or a cover. Since the size of the groove of the mold is very small, there is a high risk of damage to the manufactured microneedle patch when it is separated from the groove. A high-quality microneedle patch can be manufactured.
  • FIG. 13 is a flowchart illustrating a method for manufacturing a microneedle patch according to another embodiment of the present invention
  • FIGS. 14 and 15 are diagrams illustrating the method for manufacturing a microneedle patch of FIG. 13 .
  • the method of manufacturing a microneedle patch includes injecting a first base material into a first mold (S10), curing the first base material to form a core (S20), and Injecting a second base material into a mold (S30), curing the second base material to form a cover having an insertion groove (S40), and inserting the core into the insertion groove of the cover (S50). ) may be included.
  • the step of injecting the first base material into the first mold (S10) and the step of curing the first base material to form a core (S20) are the same as the microneedle manufacturing method of the above-described embodiment, so descriptions thereof are omitted. do it with
  • the second base material BM2 may be injected into the space between the second mold MD2 and the third mold MD3 .
  • the second mold MD2 may have a second groove MG2, and the third mold MD3 may have a protruding pin MP.
  • the protruding plate MP may have a shape and volume corresponding to that of the core 121 .
  • the second base material BM2 is filled up to a predetermined height in the second groove MG2, and the third mold MD3 is assembled to the second mold MD2.
  • the second base material BM2 disposed between the second mold MD2 and the third mold MD3 is cured. can do.
  • the outer shape of the cover 122 may be formed by the second groove MG2, and the insertion groove 122-CH may be formed by the protruding pin MP.
  • the cover 122 can be easily separated from the mold by the contractility of the second base material BM2. Since the second base material BM2 shrinks during curing, the adhesive force between the surface of the second groove MG2 and the second base material BM2 decreases. Also, the adhesive force between the surface of the protruding pin MP and the second base material BM2 is reduced.
  • the microneedle 120 may be formed by inserting the core 121 into the cover 122.
  • the core 121 may have a diameter of D1, and the insertion groove 122-CH may have an inner diameter of D2.
  • D1 and D2 are set to be substantially the same, and the core 121 may be coupled to the insertion groove 122-CH by an interference fit.
  • the intermediate material (M) may be injected into the outer surface of the core 121 or the insertion groove 122-CH of the cover 122.
  • the intermediate material M may be sprayed using the nozzle 20 .
  • the intermediate material M may be disposed between the core 121 and the cover 122 to form an intermediate layer or an intermediate region.
  • the intermediate material M may melt the first base material BM1 or the second base material BM2.
  • the size of D1 may be reduced by melting the first base material BM1.
  • the size of D2 may be increased by melting the second base material BM2. Since the intermediate material M melts the first base material BM1 or the second base material BM2, the core 121 can be easily inserted into the insertion groove 122-CH.
  • the intermediate material M may have adhesion to the first base material BM1 and the second base material BM2.
  • the intermediate material (M) is disposed and cured between the core 121 and the cover 122, it is possible to strengthen the bonding force between the core 121 and the cover 122.
  • the method for manufacturing a microneedle patch according to the present invention may manufacture a microneedle having a plurality of layers in a radial direction. Since the core 121 and the cover 122 are assembled after each manufacturing, the microneedle 120 can be manufactured simply and accurately.
  • the adhesive force between the microneedle and the mold is reduced due to the contraction of the microneedle, so that a high-quality microneedle patch can be manufactured.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Medical Informatics (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

La présente invention comprend un procédé de fabrication d'un timbre à micro-aiguilles, le procédé comprenant les étapes consistant à : injecter un premier matériau de base dans un premier moule ; faire durcir le premier matériau de base pour former une partie centrale ; insérer la partie centrale dans un second moule et injecter un second matériau de base dans le second moule ; et faire durcir le second matériau de base pour former un élément de recouvrement disposé à l'extérieur de la partie centrale.
PCT/KR2022/001927 2021-12-20 2022-02-08 Procédé de fabrication de timbre à micro-aiguilles WO2023120808A1 (fr)

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Application Number Priority Date Filing Date Title
KR1020210182373A KR20230093605A (ko) 2021-12-20 2021-12-20 마이크로니들 패치 제조 방법
KR10-2021-0182373 2021-12-20

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WO2023120808A1 true WO2023120808A1 (fr) 2023-06-29

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180009729A (ko) * 2017-09-29 2018-01-29 부산대학교 산학협력단 마이크로니들, 이의 제조 방법, 및 이를 포함하는 패치
KR20190004343A (ko) * 2016-06-07 2019-01-11 후지필름 가부시키가이샤 마이크로니들 어레이
KR20190012397A (ko) * 2017-07-27 2019-02-11 주식회사 쿼드메디슨 마이크로 니들 제조방법
US20190269895A1 (en) * 2018-03-05 2019-09-05 University Of Connecticut Core-shell microneedle platform for transdermal and pulsatile drug/vaccine delivery and method of manufacturing the same
KR20210145880A (ko) * 2020-05-25 2021-12-03 가천대학교 산학협력단 마이크로 니들 및 이의 제조방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20190004343A (ko) * 2016-06-07 2019-01-11 후지필름 가부시키가이샤 마이크로니들 어레이
KR20190012397A (ko) * 2017-07-27 2019-02-11 주식회사 쿼드메디슨 마이크로 니들 제조방법
KR20180009729A (ko) * 2017-09-29 2018-01-29 부산대학교 산학협력단 마이크로니들, 이의 제조 방법, 및 이를 포함하는 패치
US20190269895A1 (en) * 2018-03-05 2019-09-05 University Of Connecticut Core-shell microneedle platform for transdermal and pulsatile drug/vaccine delivery and method of manufacturing the same
KR20210145880A (ko) * 2020-05-25 2021-12-03 가천대학교 산학협력단 마이크로 니들 및 이의 제조방법

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